A PHASE III TRIAL OF ALD-101 ADUVANT THERAPY of UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT) IN PATIENTS WITH INBORN ERRORS OF METABOLISM

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

1. Patients must have a confirmed diagnosis of inborn error of metabolism. Diagnosis to be confirmed by two appropriate tests (enzyme or mutation analysis) before study entry.
Inborn errors of metabolism include the following:
• Hurler Syndrome (MPS I)
• Hurler-Scheie Syndrome
• Hunter Syndrome (MPS II)
• Sanfilippo Syndrome (MPS III)
• Maroteau-Lamy Syndrome (MPS VI)
• Krabbe Disease (Globoid Leukodystrophy)
• Metachromatic Leukodystrophy (MLD)
• Adrenoleukodystrophy ALD and AMN)
• Sandhoff Disease
• Tay Sachs Disease
• Pelizaeus Merzbacher (PMD)
• Neiman-Pick Disease
• Alpha-mannosidosis
2. Patients must be <16 years of age at the time of study enrollment.
3. Patients must be = 5 kg in weight.
4. Patients must have a good performance status (Lansky =80%).
5. Patients must have adequate function of other organ systems as measured by:
• Creatinine < 2.0 mg/dl and creatinine clearance > 60 cc/min/1.73m2. Newborns must have a creatinine clearance > 25 cc/min. For babies < 3 months of age, the raw value on GFR must be > 1 cc/kg/min.
• Hepatic transaminases (ALT/AST) <4 x normal, bilirubin <2.0mg/dl
• Cardiac function by echocardiogram or radionuclide scan (ejection fraction or shortening fraction >80% of normal value for age)
• Pulmonary function tests demonstrating FVC, CVC or FEV1 of >60% of predicted for age. If child is too young for PFTs, the option of crying vial capacity (CVC) testing is recommended. If CVC is not available at the investigational site, a room air pulse oxymetry oxygen = 94% will be required to meet entry criteria.
6. Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.
7. Patients must have a minimum life expectancy of at least 6 months.
8. Patient must be determined to be a good candidate for a standard UCBT according to the investigator and standard eligibility work-up at the site.
9. Patients must have an IQ >70 or if too young for IQ testing the potential to reach this endpoint by age 5.
10. Patient must have an available 4, 5, or 6/6 antigen matching unrelated UCB unit cryopreserved in a compartmentalized bag that will deliver a cell dose between =2.5 x 10e7cells/kg from one fraction (based on the precryopreservation cell content). The cord blood unit must be stored in a dual compartment bag or 2 bags to enable manufacturing ALD-101 prior to conventional transplantation.
11. Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, no menses for the previous 12 months, or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with existing vasectomy).

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients that are HIV, Hepatitis B and/or Hepatitis C positive.
2. Patients that are concurrently involved in any other clinical study that affects engraftment or immune reconstitution (e.g., other hematopoietic growth factors).
3. Patients with uncontrolled seizures, apnea, evidence of aspiration pneumonia, or evidence of brain stem involvement on MRI scans.
4. Patients with uncontrolled infections.
5. Patients with prior allogeneic stem cell transplant with cytoreduction preparative therapy within 12 months of enrollment.
6. Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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